ABSTRACT ? Co-occurring ADHD in young children with ASD: Precursors, detection, neural signatures, and early treatment Attention deficit hyperactivity disorder (ADHD) occurs in ~40-60% of individuals with autism spectrum disorder (ASD) and substantially contributes to poorer clinical outcomes. Yet, very little research has focused on the overlap of ASD and ADHD during early childhood. Thus, little is known about how these two conditions co- emerge early in life. Given the high prevalence and clinical impact of the comorbidity of ASD and ADHD, the overall goal of the Duke Autism Center of Excellence is to characterize how co-occurring ADHD influences early screening, neural signatures, developmental trajectories, and response to early treatment of young children with ASD. Project 1 will characterize risk factors for and emergence of co-occurring ADHD symptoms in young children at risk for ASD and examine how these symptoms influence early detection and progression of ASD. This project will clarify why children who have co-occurring ADHD are diagnosed at a much later age and inform more effective early detection strategies. Following a large sample of toddlers receiving routine care in Duke pediatric primary clinics (N = ~ 2800 patients/year), Project 1 will prospectively identify children at risk for ASD and collect data on risk factors, ADHD, and developmental outcomes. Project 2 will elucidate shared and distinct neural signatures and attention-related biomarkers related to ASD and ADHD, examine the functional impact of co-occurring ADHD in young children with ASD, and identify precursor characteristics during infancy that are predictive of later emergence of comorbid ASD and ADHD. This project will characterize children with ASD alone, ASD+ADHD, ADHD alone, and typically-developing children, using state-of-the-art methods, including neurophysiology, eye-tracking, movement-tracking, and computer vision analysis. Project 3 will evaluate a novel early intervention model personalized for young children with ASD+ADHD that pharmacologically addresses ADHD symptoms prior to initiating early behavioral intervention, and identify changes in behavioral and neurophysiological activity that may underlie response to treatment. This project will accomplish these goals by evaluating whether stimulant treatment (Adzenys-XR-ODT) augments the efficacy of a parent-delivered behavioral intervention based on the Early Start Denver Model. This project will examine whether changes in outcome are correlated with improvements in social attention, measured via eye-tracking biomarkers, and social engagement during parent-child interaction. This project will also examine neurophysiological changes underlying improvements in behavior. These projects will be supported by four cores: Administrative Core, Recruitment and Assessment Core, Data Management and Analysis Core, and Dissemination and Outreach Core. Functioning as a whole, the Duke Autism Center of Excellence will offer the most comprehensive understanding to date of the impact of ADHD on young children with ASD, providing important information that will allow for biologically informed and personalized methods for early detection and treatment that could mitigate the negative impact of co-occurring ADHD on individuals with ASD.